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Table 3 Current glucose-lowering therapies and their key attributes.

From: Translating recent results from the Cardiovascular Outcomes Trials into clinical practice: recommendations from the Central and Eastern European Diabetes Expert Group (CEEDEG)

Class Beneficial effect on CV outcomes Beneficial effect on HbA1c levels Effect on weight Hypoglycaemic risk
Metformin (oral) Moderate (long-term) Moderate Moderate decrease Neutral
SGLT2 inhibitors (oral)
 Empagliflozin e High (empagliflozin and canagliflozin) Moderate to high High decrease Neutral
GLP-1 receptor agonists (injection)
 Liraglutide High (liraglutide and semaglutide) High Very high decrease Neutral
 Exenatide LAR
DPP-4 inhibitors (oral)
 Sitagliptin e Neutral Moderate Neutral Neutral
Insulins (injection)
 Insulin degludec Neutral High Neutral High
 Insulin glargine
TZDs (oral)
 Pioglitazone High?b Moderate?c Increased  
SUs (oral)
 Gliclazide Neutral Moderate Neutral Moderate
  1. Agents in italics have a higher level of evidence for reduction of micro- and macrovascular complications and mortality or fewer side-effects
  2. CV cardiovascular, DPP-4 dipeptidyl peptidase 4, GLP-1 glucagon-like peptide 1, LAR long-acting release, SGLT2 sodium–glucose co-transporter 2, SU sulfonylurea, TZD thiazolidinedione
  3. aA meta-analysis of the CV safety of dulaglutide in patients with T2D [52]
  4. bAstudy that predates the CVOT mandate demonstrated significant reduction in a CV composite outcome. The study was a post hoc analysis of a prospective clinical trial [41, 53]
  5. cA double-blind, randomised trial that compared pioglitazone with metformin as monotherapies found that the HbA1c reduction was similar between the two drugs [42, 54]
  6. dAn observational prescription-event monitoring study that showed treatment with pioglitazone was associated with a low incidence of hypoglycaemia [43, 55]
  7. eAlso available in combination with metformin